Method for controlling dental caries and treating teeth sensitivity

ABSTRACT

A tooth paste composition comprising black cumin oil (Nigella sativa) and fluoride-doped bioactive glass, zinc oxide, and/or titanium oxide is disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a Continuation of U.S. application Ser. No.16/252,039, now allowed, having a filing date of Jan. 18, 2019.

BACKGROUND OF THE INVENTION Field of the Disclosure

This disclosure relates to a toothpaste composition comprisingfluoride-doped bioactive particles having antibacterial activity.

Description of the Related Art

The “background” description provided herein is for the purpose ofgenerally presenting the context of the disclosure. Work of thepresently named inventors, to the extent it is described in thisbackground section, as well as aspects of the description which may nototherwise qualify as prior art at the time of filing, are neitherexpressly or impliedly admitted as prior art against the presentinvention.

Dental caries is an infectious disease induced by diet that results inthe destruction of hard dental tissue [Harris et al. Risk factors fordental caries in young children: a systematic review of the literature,Community dental health 21 (1 Suppl) (2004) 71-85]. It affects 60-90% ofschool-aged children in most industrialized countries and a majorportion of adults [Petersen et al. The global burden of oral diseasesand risks to oral health, Bulletin of the World Health Organization 83(2005) 661-669]. The surface of an infected tooth is covered with plaqueconsisting of a bacterial film which produces acids as byproducts ofbacterial metabolism. Calcium phosphate mineral of tooth enamel ordentin is dissolved by acids in a process called demineralization. Theother common disease related to oral cavity is periodontal disease whichcan be a hereditary or acquired disorder of the periodontium, i.e.,tissues surrounding and supporting the teeth [Armitage, P. E.Periodontal diagnoses and classification of periodontal diseases,Periodontology 2000 34 (2004) 9-21]. Periodontal diseases are caused byplaque or biofilm which is the principal etiological factor leading tothe diseases. Thus, plaque control is required for prevention ofdiseases related to plaque buildup. Plaque control is achieved bymechanical means and chemical treatment and carried out by self-careand/or hygienists or dentists [Axelsson et al. The long-term effect of aplaque control program on tooth mortality, caries and periodontaldisease in adults. Results after 30 years of maintenance, Journal ofclinical periodontology 31(9) (2004) 749-57]. Dentifrice, i.e.,toothpaste, is used with a toothbrush to clean and/or polish the teeth.It aids the toothbrush in cleaning the teeth surfaces and as deliveryvehicle for one or more therapeutic agents. Dentifrices are formulatedwith several ingredients including abrasive substances, surfactants,humectants, thickeners, flavoring agents, preservatives, colors, filmagents, and sweeteners as well as one or more therapeutic agentseffective in controlling plaque and gingivitis. The therapeutic agentsmay have an antimicrobial or anti-inflammatory activity to increase theefficacy of tooth brushing. The mechanical action of the toothbrush willdecrease the amount of biofilm and disrupt its structure therebyproviding direct access of the therapeutic agents to the tooth surfaceand surrounding tissues [Sanz et al. Antiplaque and antigingivitistoothpastes, Monographs in oral science 23 (2013) 27-44]. Fluoride, ananti-caries agent, is an essential component of toothpaste. Toothpastetypically contains an amount of fluoride in the range of 500 and 1,500ppm in the form of sodium monofluorophosphate (MFP), sodium fluoride(NaF) or combination thereof. Also, toothpastes formulated with stannousfluoride (SnF₂) and amino fluoride (AmF) are known [Twetman et al.Caries-preventive effect of fluoride toothpaste: a systematic review,Acta odontologica Scandinavica 61(6) (2003) 347-55].

De-sensitizing toothpastes, mouthwashes, and chewing gums are employedfor treatment of dentinal hypersensitivity (DH). It may be defined asshort, sharp pain arising from exposed dentin in response to stimuli,typically thermal, evaporative, tactile, osmotic or chemical and whichcannot be ascribed to any other dental defect or pathology [Holland etal. Guidelines for the design and conduct of clinical trials on dentinehypersensitivity, Journal of clinical periodontology 24(11) (1997)808-13]. In recent years, various studies have shown hydroxyapatitenanoparticles (nano-HA) as a biomimetic material for re-constructingtooth enamel suffering from mineral loss. Because of its uniquepotential for remineralization, it has been considered as an effectiveanti-caries agent [Yamagishi et al. Materials chemistry: a syntheticenamel for rapid tooth repair, Nature 433(7028) (2005) 819, Li et al.Tang, Repair of enamel by using hydroxyapatite nanoparticles as thebuilding blocks, Journal of Materials Chemistry 18(34) (2008) 4079-4084;Roveri et al. Surface Enamel Remineralization: Biomimetic ApatiteNanocrystals and Fluoride Ions Different Effects, Journal ofNanomaterials 2009 (2009) 9; and Hannig et al. Nanomaterials inpreventive dentistry, Nature nanotechnology 5(8) (2010) 565-9]. Also,studies have reported the potential of nano-HA to remineralizeartificial carious lesions following addition to toothpastes,mouthwashes, and other dental care products [Yamagishi et al. (2005),and Gao et al. Effect of nano-hydroxyapatite concentration onremineralization of initial enamel lesion in vitro, Biomedical materials(Bristol, England) 4(3) (2009) 034104].

Prof. L. L. Hench introduced the first bioactive glass in 1969 havingthe composition of 46.1 mol. % SiO₂, 24.4 mol. % Na₂O, 26.9 mol. % CaOand 2.6 mol. % P₂ O₅ (later termed 45S5 and Bioglass®). Bioactive glassforms a strong bond with bone [Hench, L. L. The story of Bioglass®,Journal of Materials Science: Materials in Medicine 17(11) (2006)967-978]. It has been incorporated into toothpastes because of itspotential for remineralization and antibacterial properties as well asfor the treatment of hypersensitivity [Abbasi et al. Bioactive Glassesin Dentistry: A Review, J Dent Biomater 2 (1) (2015) 1-9].

NovaMin® (NovaMin Technology, GlaxoSmithKline, Florida, UK) is a veryfine Bioglass® particulate. It has a particle size of ˜18 μm and is usedas an active repair agent in toothpaste. It reduces dentinhypersensitivity by mineralizing tiny holes in the dentin [Jones, J. R.Review of bioactive glass: From Hench to hybrids, Acta biomaterialia9(1) (2013) 4457-4486]. When these types of toothpastes are used,Bioglass® particles adhere to the dentin and form apatite layer that issimilar in composition to enamel and block dentinal tubules leading torelieving pain for longer periods of time [Gillam et al. The effects ofa novel Bioglass dentifrice on dentine sensitivity: a scanning electronmicroscopy investigation, Journal of oral rehabilitation 29(4) (2002)305-13]. They are generally introduced into various toothpastes as veryfine particles to provide calcium and phosphorus to the tooth surface[Madan et al. Tooth remineralization using bio-active glass-A novelapproach, Journal of Advanced Dental Research 2(2) (2011) 45]. Variousstudies have shown the remineralization potential of bioactive glassesincorporated in toothpastes [Vollenweider et al. Remineralization ofhuman dentin using ultrafine bioactive glass particles, Actabiomaterialia 3(6) (2007) 936-43; and Wang et al. The dentineremineralization activity of a desensitizing bioactive glass-containingtoothpaste: an in vitro study, Australian dental journal 56(4) (2011)372-81].

Toothpastes require a certain degree of abrasivity to perform thecleaning action. However, abrasivity of toothpastes needs to bemoderated in order to prevent the wearing of underlying enamel anddentin. Thus, toothpaste manufacturers aim at minimizing hard tissuedamage while maximizing cleaning efficiency [Joiner et al. Whiteningtoothpastes: effects on tooth stain and enamel, International DentalJournal 52 (S5) (2002) 424-430]. The wear produced by toothpastes,toothbrushes, and polishing pastes is defined as abrasion in contrast totooth-to-tooth contact wear which is defined as attrition.

In addition to abrasive agents various types of natural and/or herbalproducts have been used in dentifrices including extracts fromsanguinarine, chamomile, sage, rhatany, myrrh, echinacea, andpeppermint. Sanguinarine, an alkaloid extracted from the plantSanguinaria canadensis has low bactericidal activity, and in combinationwith zinc chloride can significantly reduce plaque and gingivitis [Sanzet al. (2013)].

It is therefore one object of the present disclosure to provide a newdentifrice (toothpaste) with both synthetic and herbal activeingredients having low abrasivity. The active ingredients have abilityto remineralize the tooth structure and contain antibacterialproperties.

BRIEF SUMMARY OF THE INVENTION

According to a first aspect, the present disclosure relates totoothpaste composition comprising:

(a) black cumin oil (Nigella sativa) in the range of 0.1 wt. % to 6 wt.%,

(b) an amount of water in the range of 33 wt. % to 36 wt. %;

(c) a surfactant in the range of 1 wt. % to 2 wt. %,

(d) a humectant in the range of 29 wt. % to 32 wt. %,

(e) a preservative in the range of 0.5% to 1.0 wt. %,

(f) a thickening agent in the range of 0.5% to 1.0 wt. %,

(g) an abrasive agent in the range of 24 wt. % to 27 wt. %, and

(h) a flavoring agent in the range of 0.5% to 1.0 wt. %;

wherein the wt. % is the percent by weight of the total weight of thetoothpaste.

In a preferred embodiment, the toothpaste comprises fluoride-dopedbioactive glass in the range of 0.1 wt. % to 4.0 wt. % of the totalweight of the tooth paste.

In another preferred embodiment, the toothpaste comprises an amount zincoxide in the range of 0.1 wt. % to 3.0 wt. % of the total weight of thetooth paste.

In another preferred embodiment, the toothpaste comprises titanium oxideand zinc oxide in an amount in the range of 0.1 wt. % to 2.0 wt. % andfluoride-doped bioactive glass in an amount in the range of 0.1 to 4.0wt. % of the total weight of the toothpaste.

In another preferred embodiment, the toothpaste comprises water in anamount of about 36 wt. % of the total weight of the total weight of thetoothpaste.

In another preferred embodiment, the surfactant is sodium lauryl sulfate(SLS) in an amount in the range of 1 wt. % to 2 wt. % of the totalweight of the toothpaste.

In another preferred embodiment, the humectant is glycerol in an amountof in the range of 29 wt. % to 32 wt. % of the total weight of thetoothpaste.

In another preferred embodiment, the preservative is sodium benzoate inan amount of about 1 wt. % of the total weight of the toothpaste.

In another preferred embodiment, the thickening agent is methylcellulosein an amount in the range of 0.5 wt. % to 1 wt. % of the total weight ofthe toothpaste.

In another preferred embodiment, the abrasive agent is calcium carbonatein an amount in the range of 24 wt. % to 27 wt. % of the total weight ofthe toothpaste.

In a more preferred embodiment, the toothpaste composition comprisesflavoring agent in an amount of about 1 wt. % of the total weight of thetoothpaste.

In a more preferred embodiment, the toothpaste composition comprises:

-   -   black cumin oil (Nigella sativa) in the range of 0.1 wt. % to 6        wt. %,    -   an amount of water in the range of 33 wt. % to 36 wt. %;    -   sodium lauryl sulfate (SLS) in the range of 1 wt. % to 2 wt. %,    -   glycerol in the range of 29 wt. % to 32 wt. %,    -   sodium benzoate in the range of 0.5% to 1.0 wt. %,    -   methyl cellulose in the range of 0.5% to 1.0 wt. %,    -   calcium carbonate in the range of 24 wt. % to 27 wt. %,    -   flavoring agent in the range of 0.5% to 1.0 wt. %,    -   fluoride-doped bioactive glass in the range of 0.1 wt. % to 4.0        wt. %,    -   zinc oxide in an amount in the range of 0.1 wt. % to 3.0 wt. %,        and    -   titanium oxide in an amount in the range of 0.1 wt. % to 3.0 wt.        %;

wherein the wt. % is the present by weight of the total weight of thetoothpaste.

According to the second aspect of invention, the disclosure is directedto a method of controlling dental caries and treating teeth sensitivitycomprises: contacting the teeth of a subject with the tooth pastedisclosed herein and brushing the teeth.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete appreciation of the disclosure and many of the attendantadvantages thereof will be readily obtained as the same becomes betterunderstood by reference to the following detailed description whenconsidered in connection with the accompanying drawings, wherein:

FIG. 1A shows dentine surface roughness observed by 3D-Atomic ForceMicroscope (AFM) for a negative control dentine treated with distilledwater.

FIG. 1B shows dentine surface roughness observed by 3D AFM for apositive control dentine treated with commercial toothpaste.

FIG. 1C shows dentine surface roughness observed by 3D AFM for a dentinetreated with experimental past A.

FIG. 1D shows dentine surface roughness observed by 3D AFM for a dentinetreated with experimental past B.

FIG. 1E shows dentine surface roughness observed by 3D AFM for a dentinetreated with experimental past C.

FIG. 1F shows dentine surface roughness observed by 3D AFM for a dentinetreated with experimental past D.

FIG. 1G shows dentine surface roughness observed by 3D AFM for a dentineuntreated.

FIG. 2 shows an SEM micrograph of dentin surface morphology etched with37% phosphoric acid showing open or patent dentinal tubules at ×5000magnification.

FIG. 3A shows an SEM micrograph of dentin at magnifications×5000 afterrinsing with deionized water and sonication, negative control ordistilled water.

FIG. 3B shows an SEM micrograph at a magnification of ×5000 afterrinsing with deionized water and sonication, positive control.

FIG. 3C shows an SEM micrograph of dentine treated with experimentalpaste A at a magnification of ×5000 after rinsing with deionized waterand sonicating, negative control or distilled water.

FIG. 3D shows an SEM micrograph of dentine treated with experimentalpaste B at a magnification of ×5000 after rinsing with deionized waterand sonication, negative control or distilled water.

FIG. 3E shows an SEM micrograph of dentine treated with experimentalpaste C at a magnification of ×5000 after rinsing with deionized waterand sonication, negative control or distilled water.

FIG. 3F shows an SEM micrograph of dentine treated with experimentalpaste D at a magnification of ×5000 after rinsing with deionized waterand sonication, negative control or distilled water.

DETAILED DESCRIPTION OF THE EMBODIMENTS

All publications mentioned herein are incorporated herein by referencein full for the purpose of describing and disclosing the methodologies,which are described in the publications, which might be used inconnection with the description herein. Nothing herein is to beconstrued as an admission that the inventors are not entitled toantedate such disclosure by virtue of prior disclosure. Also, the use of“or” means “and/or” unless stated otherwise. Similarly, “comprise,”“comprises,” “comprising” “include,” “includes,” and “including” areinterchangeable and not intended to be limiting.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention.

The headings such as “Background” and “Summary”, and sub-headings usedherein are intended only for general organization of topics within thepresent invention, and are not intended to limit the disclosure of thepresent invention or any aspect thereof. In particular, subject matterdisclosed in the “Background” may include novel technology and may notconstitute a recitation of prior art. Subject matter disclosed in the“Summary” is not an exhaustive or complete disclosure of the entirescope of the technology or any embodiments thereof. Classification ordiscussion of a material within a section of this specification ashaving a particular utility is made for convenience, and no inferenceshould be drawn that the material must necessarily or solely function inaccordance with its classification herein when it is used in any givencomposition.

As used herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise.

As used herein, the term “and/or” includes any and all combinations ofone or more of the associated listed items and may be abbreviated as“/”.

The terms “comprises” and/or “comprising,” when used in thisspecification, specify the presence of stated features, steps,operations, elements, and/or components, but do not preclude thepresence or addition of one or more other features, steps, operations,elements, components, and/or groups thereof.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “substantially”, “about” or“approximately,” even if the term does not expressly appear. The phrase“about” or “approximately” may be used when describing magnitude and/orposition to indicate that the value and/or position described is withina reasonable expected range of values and/or positions. For example, anumeric value may have a value that is +/−0.1% of the stated value (orrange of values), +/−1% of the stated value (or range of values), +/−2%of the stated value (or range of values), +/−5% of the stated value (orrange of values), +/−10% of the stated value (or range of values),+/−15% of the stated value (or range of values), +/−20% of the statedvalue (or range of values), etc. Any numerical range recited herein isintended to include all sub-ranges subsumed therein.

As used herein, the words “preferred” and “preferably” refer toembodiments of the technology that afford certain benefits, undercertain circumstances. However, other embodiments may also be preferred,under the same or other circumstances. Furthermore, the recitation ofone or more preferred embodiments does not imply that other embodimentsare not useful, and is not intended to exclude other embodiments fromthe scope of the technology.

As referred to herein, all compositional percentages are by weight ofthe total weight of toothpaste, unless otherwise specified. As usedherein, the word “include,” and its variants, is intended to benon-limiting, such that recitation of items in a list is not to theexclusion of other like items that may also be useful in the materials,compositions, devices, and methods of this technology. Similarly, theterms “can” and “may” and their variants are intended to benon-limiting, such that recitation that an embodiment can or maycomprise certain elements or features does not exclude other embodimentsof the present invention that do not contain those elements or features.

Disclosure of values and ranges of values for specific parameters (suchas temperatures, molecular weights, weight percentages, etc.) are notexclusive of other values and ranges of values useful herein. Two ormore specific exemplified values for a given parameter may defineendpoints for a range of values that may be claimed for the parameter.For example, if Parameter X is exemplified herein to have value A andalso exemplified to have value Z, it is envisioned that parameter X mayhave a range of values from about A to about Z. Similarly, it isenvisioned that disclosure of two or more ranges of values for aparameter (whether such ranges are nested, overlapping or distinct)subsume all possible combination of ranges for the value that might beclaimed using endpoints of the disclosed ranges. For example, ifparameter X is exemplified herein to have values in the range of 1-10 itis also envisioned that Parameter X may have other ranges of valuesincluding 1-9, 2-9, 3-8, 1-8, 1-3, 1-2, 2-10, 2.5-7.8, 2-8, 2-3, 3-10,and 3-9, as mere examples.

Although the open-ended term “comprising,” as a synonym of terms such asincluding, containing, or having, is use herein to describe and claimthe present invention, the invention, or embodiments thereof, mayalternatively be described using more limiting terms such as “consistingof” or “consisting essentially of” the recited ingredients. Althoughvarious illustrative embodiments are described above, any of a number ofchanges may be made to various embodiments without departing from thescope of the invention as described by the claims. For example, theorder in which various described method steps are performed may often bechanged in alternative embodiments, and in other alternative embodimentsone or more method steps may be skipped altogether. Optional features ofvarious device and system embodiments may be included in someembodiments and not in others. Therefore, the foregoing description isprovided primarily for exemplary purposes and should not be interpretedto limit the scope of the invention as it is set forth in the claims.

The examples and illustrations included herein show, by way ofillustration and not of limitation, specific embodiments in which thesubject matter may be practiced. As mentioned, other embodiments may beutilized and derived there from, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. Such embodiments of the inventive subject matter maybe referred to herein individually or collectively by the term“invention” merely for convenience and without intending to voluntarilylimit the scope of this application to any single invention or inventiveconcept, if more than one is, in fact, disclosed. Thus, althoughspecific embodiments have been illustrated and described herein, anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description.

A first aspect of the invention is directed a toothpaste compositioncomprises water, surfactant, humectant, thickening agent, abrasiveagent, preserving agent, and flavoring agent. Also, the toothpastecomposition may contain other ingredients such as but not limited tocoloring agent, anticalculus agent, vitamins, sweetener, enzymes such asproteases and amylases, antioxidant, silicones, desensitizer such aspotassium nitrate, whitening agent such as hydrogen peroxide, calciumperoxide, urea peroxide, clay, breath freshening agent, antibacterial,antiplaque agent, Poloxomer polymers such as POLOXOMER 407, PLURONICF108, (both available from BASF Corporation), polymers, polyglycoside(APG), chlorophyll compound, bicarbonate salts, and viscosity modifier.Also, basic amino acids such as but are not limited to arginine, lysine,citrulline, ornithine, creatine, histidine, diaminobutanoic acid,diamine propionic acid, salts thereof and combinations thereof may beincluded in the toothpaste.

The toothpaste composition of the invention comprises water in an amountin the range of 20% to 50%, preferably in the range of 25 to 40%, morepreferably in the range 30% to 38%, and most preferably about 36% byweight of the total weight of the toothpaste composition and at leastone surfactant.

The surfactant is useful for example to compatibilize other componentsof the composition and thereby provide enhanced stability as well as toaid in cleaning the dental surface through detergency and provide foamupon agitation, e.g., during brushing with a dentifrice composition ofthe invention. Any orally acceptable surfactant, most of which areanionic, cationic, nonionic, zwitterionic, or amphoteric, or mixturethereof can be used.

Suitable anionic surfactants include without limitation water-solublesalts of C₈₋₂₀ alkyl sulfates, sulfonated monoglycerides of C₈₋₂₀ fattyacids, sarcosinates, taurates, and the like. Illustrative examples ofthese and other classes include sodium dodecyl benzene sulfonate, sodiumlauryl sulfate, sodium ether lauryl sulfate, sodium coconutmonoglyceride sulfonate, sodium lauryl sarcosinate, sodium laurylisoethionate, sodium laureth carboxylate, and sodium dodecylbenzenesulfonate.

Suitable cationic surfactants useful in the oral compositions of thepresent invention can be broadly defined as quaternary ammoniumcompounds having one long alkyl chain containing from about 8 to about18 carbon atoms such as lauryl trimethylammonium chloride; cetylpyridinium chloride; cetyl trimethylammonium bromide;di-isobutylphenoxyethoxyethyl-dimethylbenzylammonium chloride;coconutalkyltrimethylammonium nitrite; cetyl pyridinium fluoride; etc.Especially preferred are the quaternary ammonium fluorides described inU.S. Pat. No. 3,535,421 incorporated by reference hereinbefore in itsentirety, where said quaternary ammonium fluorides have detergentproperties.

Suitable nonionic surfactants include without limitation poloxamers suchas POLOXOMER 407 and PLURONIC F108 (both available from BASFCorporation), polyoxyethylene sorbitan esters, fatty alcoholethoxylates, alkylphenol ethoxylates, tertiary amine oxides such as butnot limited to dodecyldimethylphosphine oxide,tetradecyldimethylphosphine oxide, tetradecylmethylethylphosphine oxide,3,6,9-trioxaoctadecyldimethylphosphine oxide, cetyldimethylphosphineoxide, 3-dodecoxy-2-hydroxy-propyldi(2-hydroxyethyl)phosphine oxide,stearyldimethylphosphine oxide, cetylethylpropyl-phosphine oxide,oleyldiethylphosphine oxide, dodecyldiethylphosphine oxide,tetradecyldiethylphosphine oxide, dodecyldipropyiphosphine oxide,dodecyldi(hydroxymethyl)phosphine oxide,dodecyldi(2-hydroxyethyl)phosphine oxide,tetradecylmethyl-2-hydroxypropylphosphine oxide, oleyldimethylphosphineoxide, 2-hydroxydodecyldimethylphosphine oxide, tertiary phosphineoxides such as but not limited to dodecyldimethylphosphine oxide,tetradecyldimethylphosphine oxide, tetradecylmethylethylphosphine oxide,3,6,9-trioxaoctadecyldimethylphosphine oxide, cetyldimethylphosphineoxide, 3-dodecoxy-2-hydroxy-propyldi(2-hydroxyethyl)phosphine oxide,stearyldimethylphosphine oxide, cetylethyl-propylphosphine oxide,oleyldiethylphosphine oxide, dodecyldiethylphosphine oxide,tetradecyldiethylphosphine oxide, dodecyldipropyiphosphine oxide,dodecyldi(hydroxyl-methyl)phosphine oxide,dodecyldi(2-hydroxyethyl)phosphine oxide,tetradecylmethyl-2-hydroxypropylphosphine oxide, oleyldimethylphosphineoxide, 2-hydroxydodecyldimethylphosphine oxide, dialkyl sulfoxides suchas but not limited to octadecyl methyl sulfoxide, 2-ketotridecyl methylsulfoxide, 3,6,9-trioxaoctadecyl 2-hydroxyethyl sulfoxide, dodecylmethyl sulfoxide, oleyl 3-hydroxy propyl sulfoxide, tetradecyl methylsulfoxide, 3-methoxytridecyl methyl sulfoxide 3-hydroxytridecyl methylsulfoxide, 3-hydroxy-4-dodecoxybutyl methyl sulfoxide and the like.

Zwitterionic synthetic detergents useful in the oral compositions of thepresent invention can be broadly described as derivatives of aliphaticquaternary ammonium, phosphonium, and sulfonium compounds, in which thealiphatic radicals can be straight chain or branched, and wherein one ofthe aliphatic substituents contains from about 8 to 18 carbon atoms andone contains an anionic water solubilizing group, e.g., carboxy,sulfonate, sulfate, phosphate, or phosphonate. Examples include:4-[N,N-di(2-hydroxyethyl)-N-octadecylammonio]-butane-1-carboxylate;5-]S-3-hydroxypropyl-S-hexadecylsulfonio]-3-hydroxypentane-1-sulfate;3-[P,P-diethyl-P-3,6,9-trioxatetradecoxylphosphonio]-2-hydroxypropane-1-phosphate;3-[N,N-dipropyl-N-3-dodecoxy-2-hydroxypropylammonio]-propane-1-phosphonate;3-(N,N-dimethyl-N-hexa-decylammonio)propane-1-sulfonate;3-(N,N-dimethyl-N-hexadecylammonio)-2-hydroxy-propane-1-sulfonate;4-[N,N-di(2-hydroxyethyl)-N-(2-hydroxydodecyl)ammonio]butane-1-carboxylate;3-[S-ethyl-S-(3-dodecoxy-2-hydroxypropyl)sulfonio]-propane-1-phosphate;3-[-P,P-dimethyl-P-dodecylphosphonio]-propane-1-phosphonate; and5-[N,N-di(3-hydroxypropyl)-N-hexadecylammonio]2-hydroxypentane-1-sulfate.

Suitable amphoteric surfactants include without limitation derivativesof C₈₋₂₀ aliphatic secondary and tertiary amines having an anionic groupsuch as carboxylate, sulfate, sulfonate, phosphate or phosphonate.Examples of compounds falling within this definition are sodium3-dodecylaminopropionate, sodium 3-dodecylaminopropane sulfonate,dodecyl-beta-alanine, cocoamidopropyl betaine, N-alkyl-taurines such asthe one prepared by reacting dodecylamine with sodium isethionateaccording to the teaching of U.S. Pat. No. 2,658,072, N-higher alkylaspartic acids such as disclosed in U.S. Pat. No. 2,438,091, and theproducts sold under the trade name “Miranol” and described in U.S. Pat.No. 2,528,378.

The amount of one or more surfactants are present in a total amount inthe range of 0.01% to 10%, preferably in the range of 0.05% to 5%, morepreferably 1.0% to 4.0%, and most preferably in the range of 1.5% to2.5% by weight of the total weight of the toothpaste composition.

In a preferred embodiment, the toothpaste composition comprises sodiumlauryl sulfate (SLS) in an amount in the range of 0.1% to 10%, andpreferably in the range of 0.5% to 5%, more preferably in the range of1.0 to 3%, and most preferably about 2% by weight of the total weight oftoothpaste composition.

Also, the toothpaste composition of the invention comprises at least onethickening agent, useful for example to impart a desired consistencyand/or mouth feel to the composition. Any orally acceptable thickeningagent can be used, including without limitation carbomers, also known ascarboxyvinyl polymers, carrageenans, also known as Irish moss, and moreparticularly t-carrageenan (iota-carrageenan), cellulosic polymers suchas methylcellulose, hydroxyethyl-cellulose, carboxymethylcellulose (CMC)and salts thereof, e.g., CMC sodium, natural gums such as karaya,xanthan, gum Arabic and tragacanth, colloidal magnesium aluminumsilicate, colloidal silica and the like. One or more thickening agentsare present in a total amount in the range of 0.01% to 10%, preferablyin the range of 0.1% to 5%, more preferably in the range of 0.2% to1.5%, and most preferably 0.5% to 1.0% by weight of the total weight ofthe toothpaste composition.

In a preferred embodiment, the toothpaste composition comprisesmethylcellulose in an amount in the range of 0.01% to 10%, preferably inthe range of 0.1% to 5%, more preferably in the range of 0.2% to 1.5%,and most preferably 0.5% to 1.0% by weight of the total weight of thetoothpaste composition. In a particularly preferred embodiment, thetoothpaste composition comprises about 1% by weight of the totalcomposition of the toothpaste composition.

In another preferred embodiment, the toothpaste composition of theinvention comprises at least one humectant, useful for example toprevent hardening of toothpaste upon exposure to air. Any orallyacceptable humectant can be used, including without limitationpolyhydric alcohols such as glycerin, sorbitol, xylitol, butyleneglycol, propylene glycol, polyethylene glycol, other edible polyhydricalcohol, or low molecular weight PEGs, and combinations thereof. Also,most humectants function as sweeteners. A humectant is present in thecomposition in an amount in the range of 5% to 60%, preferably in therange of 10% to 50%, more preferably in the range of 20% to 35%, andmost preferably in the range of 25% to 33% by weight of the total weightof the toothpaste composition. In a particularly preferred embodiment,the humectant is glycerol added to the toothpaste composition in anamount in the range of 29% to 32%, preferably about 32% by weight of thetotal weight of the toothpaste composition.

In another preferred embodiment, the toothpaste composition of theinvention comprises at least one abrasive, useful for example as apolishing agent. Any orally acceptable abrasive can be used, but type,particle size and amount of abrasive should be selected so that toothenamel is not excessively abraded in normal use of the composition.Suitable abrasives include without limitation silica, for example in theform of silica gel, hydrated silica or precipitated silica, alumina,insoluble phosphates, calcium carbonate, resinous abrasives such asurea-formaldehyde condensation products and the like. Among insolublephosphates useful as abrasives are orthophosphates, polymetaphosphates,and pyrophosphates. Illustrative examples are dicalcium orthophosphatedihydrate, calcium pyrophosphate, calcium pyrophosphate, tricalciumphosphate, calcium polymetaphosphate and insoluble sodiumpolymetaphosphate. In a particularly preferred embodiment, calciumcarbonate is used alone or in combination with other suitable abrasivematerial. The abrasive is present in the toothpaste compositing in aneffective amount, typically in the range of 10% to 60%, preferably inthe range of 15% to 40%, more preferably in the range 20% to 30%, andmost preferably in the range 24% to 27% of by weight of the total weightof the toothpaste composition. Average particle size of an abrasive isgenerally in the range of 0.1 to 30 μm, preferably I the range of 1 to20 μm, and more preferably in the range of 5 to 15 μm.

In a particularly preferred embodiment, the abrasive is calciumcarbonate added to the toothpaste composition in an amount in the rangeof 20% to 35%, preferably in the range 25% to 30%, more preferably inthe range of 26% to 28%, and most preferably about 27% by weight of thetotal weight of the toothpaste composition.

In some embodiments, the toothpaste composition of the inventioncomprises at least one bicarbonate salt, useful for example to impart a“clean feel” to teeth and gums due to effervescence and release ofcarbon dioxide. Any orally acceptable bicarbonate can be used, includingwithout limitation alkali metal bicarbonates such as sodium andpotassium bicarbonates, ammonium bicarbonate and the like. One or morebicarbonate salts are optionally present in a total amount in the rangeof 0.1% to 20%, preferably in the range of 2% to 10% by weight of thetotal toothpaste composition.

In some embodiments, the toothpaste composition of the inventioncomprises at least one pH buffering agent in sufficient amount tomaintain the pH of the composition at a desired level. The bufferingagent is a combination of acid or base and a salt thereof. Many examplesbuffering agents are well known in the art having good pH bufferingcapacity in the pH range of 2.0 to 10.0 including but not limited tocitrate, tartrate, acetate, phosphate, glycine, carbonate, borate, andimidazole.

In some embodiments, the toothpaste composition of the inventioncontains one or more flavoring agent, useful for example to enhancetaste of the composition. Any orally acceptable natural or syntheticflavoring agent may be used, including, but not limited to, vanillin,sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil ofwintergreen (methylsalicylate), peppermint oil, clove oil, bay oil,anise oil, eucalyptus oil, citrus oils, fruit oils and essencesincluding those derived from lemon, orange, lime, grapefruit, apricot,banana, grape, apple, strawberry, cherry, pineapple, bean- andnut-derived flavors such as coffee, cocoa, cola, peanut, and almond aswell as. Also encompassed within flavoring agents herein are ingredientsthat provide fragrance and/or other sensory effect in the mouth,including cooling or warming effects. Such ingredients illustrativelyinclude menthol, menthyl acetate, menthyl lactate, camphor, eucalyptusoil, eucalyptol, anethole, eugenol, cassia, oxanone, .α-irisone,propenyl guaiethol, thymol, linalool, benzaldehyde, cinnamaldehyde,N-ethyl-p-menthan-3-carboxamine, N,2,3-trimethyl-2-isopropylbutanamide,3-(1-menthoxy)-propane-1,2-diol, cinnamaldehyde glycerol acetal (CGA),menthone glycerol acetal (MGA), natural or artificial sweetenerincluding but not limited to non-cariogenic sweeteners such assaccharin, aspartame, dextrose, and levulos, and the like. Thetoothpaste composition of the invention comprises one or more flavoringagents in a total amount in the range of 0.01% to 5%, preferably in therange of 0.1% to 3%, more preferably in the range of 0.5 to 1.5%, andmost preferably about 1%.

The toothpaste composition may contain one or more anticalculus agents.Suitable anticalculus agents include, but are not limited to, phosphatesand polyphosphates such as pyrophosphates, polyaminopropanesulfonic acid(AMPS), zinc citrate trihydrate, polypeptides such as polyaspartic andpolyglutamic acids, polyolefin sulfonates, polyolefin diphosphonatessuch as azacycloalkane-2,2-diphosphonates (e.g.,azacycloheptane-2,2-diphosphonic acid), N-methylazacyclopentane-2,3-diphosphonic acid, ethane-1-hydroxy-1,1-diphosphonicacid (EHDP) and ethane-1-amino-1,1-diphosphonate, phosphonoalkanecarboxylic acids and salts of any of these agents, for example theiralkali metal and ammonium salts. A particularly useful inorganicphosphate and polyphosphate salts include, but not limited to monobasic,dibasic and tribasic sodium phosphates, sodium tripolyphosphate,tetrapolyphosphate, mono-, di-, tri- and tetrasodium pyrophosphates,disodium dihydrogen pyrophosphate, sodium trimetaphosphate, sodiumhexametaphosphate and the like, wherein sodium can optionally bereplaced by potassium or ammonium. Other useful anticalculus agentsinclude anionic polycarboxylate polymers. The anionic polycarboxylatepolymers contain carboxyl groups on a carbon backbone and includepolymers or copolymers of acrylic acid, methacrylic, and maleicanhydride. Non-limiting examples include polyvinyl methyl ether/maleicanhydride (PVME/MA) copolymers, such as those available under theGantrez brand from ISP, Wayne, N.J. Still other useful anticalculusagents include sequestering agents including di and tricarboxylic acidsand hydroxycarboxylic acids such as citric, fumaric, malic, glutaric andoxalic acids and salts thereof, and aminopolycarboxylic acids such asethylenediaminetetraacetic acid (EDTA). One or more anticalculus agentsmay be present in the toothpaste composition in an anticalculuseffective total amount, typically in the range of 0.01% to 20%,preferably in the range of 0.1 to 15%, more preferably in the range of1% to 10% by weight of the total toothpaste composition.

Another useful additive to the toothpaste composition is a viscositymodifier, useful for example to inhibit settling or separation ofingredients or to promote re-dispensability upon agitation of a liquidcomposition. Any orally acceptable viscosity modifier can be used,including without limitation mineral oil, petrolatum, clays,organo-modified clays, silica, and the like. One or more viscositymodifiers may be added to the toothpaste composition in an amount in therange of 0.01% to 10%, preferably in the range of 0.1% to 5% by weightof the total weight of the toothpaste composition.

An orally acceptable breath freshening agent is yet another usefuladditive to the toothpaste composition. One or more such agents may beadded to the toothpaste composition in an effective amount. Suitablebreath-freshening agents include, but not limited to zinc salts such aszinc gluconate, zinc citrate and zinc chlorite, α-ionone and the like.

Preservatives, such as sodium benzoate, butylated hydroxyanisole (BHA),butylated hydroxytoluene (BHT), p-hydroxybenzoic ester, ascorbic acid,alkyldiaminoethylglycine hydrochloride, chlorhexidine, triclosan,quaternary ammonium compounds such as benzalkonium chloride, benzylalcohol, tocopherol, or parabens such as methyl, ethyl or propyl parabenmay be incorporated in the toothpaste composition. The amount ofpreservative in the toothpaste composition is typically in the range of0.1 wt. % to about 2 wt. %, preferably in the range of 0.2 wt. % to 1.5wt. %, more preferably in the range of 0.5 wt. % to 1.2 wt. % and mostpreferably about 1% of the total weight of the toothpaste composition.

As used herein, the term “active ingredient” refers to an ingredientthat has a specific function in treating and restoring the dentin andgum. For example, black cumin oil from Nigella sativa has antibacterial,anti-inflammatory, and antioxidant activities. Fluoride-doped bioactiveglass has both antibacterial and remineralization activities. Zinc oxidehas antibacterial and remineralization activity. Titanium oxide iswhitening agent.

Nigella sativa (commonly known as black cumin, black seed, or blackcurcumin) is an annual flowering plant, native to south and southwestAsia. It grows to 20-30 cm (7.9-12 in) tall, with finely divided, linearbut not thread-like leaves. The flowers are delicate, and usuallycolored pale blue and white, with five to ten petals. The fruit is alarge and inflated capsule composed of three to seven united follicles,each containing numerous seeds. The seed may be used as a spice. Nigellasativa has a pungent bitter taste and smell. Nigella sativa istraditionally used in the Indian subcontinent, the Middle East, andEurope for culinary and medicinal purposes as a natural remedy for anumber of illnesses and conditions that include asthma, hypertension,diabetes, inflammation, cough, bronchitis, headache, eczema, fever,dizziness and influenza. Much of the biological activity of the seeds isbelieved to be due to thymoquinone (TQ), the putative activephytochemical of Nigella sativa, a component of the essential oil. TQ isalso present in the fixed oil. Also, Nigella sativa oil containsconjugated linoleic (18:2) acid, nigellone (dithymoquinone), melanthin,nigilline, damascenine, and tannins.

Extracts and oil obtained from Nigella sativa are known to haveantimicrobial activity, anti-inflammatory activity and anti-oxidantactivity and have been used as additives to dental care products(US2014/0308219-incorporated in its entirety herein by reference). Also,known is the addition of oil from Nigella sativa to toothpastecompositions lubricates mouth tissues and/or treats dry mouth. Inaddition, when components found in extracts of Nigella sativa, or oilsfrom Nigella sativa are added to dentifrice compositions, theastringency of the compositions is reduced. Accordingly, one of the mainactive ingredients used in the toothpaste of the disclosed invention isan extract or black cumin oil from Nigella sativa. The extract or oil isadded to the total toothpaste in an amount in the range of 0.01% to 10%,preferably in the range 1% to 9%%, more preferably in the range 1.5% to7%, and most preferably in the range of 2% to 6% by weight of the totalweight of the toothpaste. In a preferred embodiment, black cumin oilfrom Nigella sativa is add to the toothpaste composition in an amount inthe range of 0.5% to 6% by weight of the total weight of the toothpaste.

As referred to herein, an “extract” or “oil” suitable for use in thevarious embodiments of the present invention can be obtained from anypart of Nigella sativa plant including the leaf, stem, stalk, cortex(i.e., bark), pulp, seed, flesh, juice, root, flower, or any othersuitable part of a plant or other natural source.

As used herein, “extracting” or “extraction” of a solid or liquidmaterial means contacting the material with an appropriate solvent toremove the substance(s) desired to be extracted from the material. Wherethe material is solid, it is preferably dried and crushed or groundprior to contacting it with the solvent. Such an extraction may becarried out by conventional means known to one of skill in the art, forexample, by using an extraction apparatus, such as a Soxhlet apparatus,which retains the solid material in a holder and allows the solvent toflow through the material; by blending the solvent and material togetherand then separating the liquid and solid phases or two immiscible liquidphases, such as by filtration or by settling and decanting. In variousembodiments, the botanical active ingredients used in oral carecompositions are of reproducible, stable quality and havemicrobiological safety. Black cumin oil from Nigella sativa may beobtained commercially or by extracting the oil from the plant seeds bywell-known methods in the art.

“Bioactive glass” refers to a group of surface reactive glass-ceramicsthat include the original bioactive glass, Bioglass®. Thebiocompatibility of these glasses has led them to be investigatedextensively for use as implant materials in the human body to repair andreplace diseased or damaged bone. There have been many variations on theoriginal composition which was FDA approved and termed Bioglass®, whichis also known as 45S5. As referred to herein, bioactive glasses aretypically silicon dioxide-based compositions capable of forminghydroxycarbonate apatite when exposed to physiological fluids.Typically, the bioactive glasses for use in the presently disclosedcompositions and methods have the following composition by molarpercentage:

from about 50 to about 96 mole percent SiO₂;

from about 2 to about 50 mole percent CaO;

from about 2 to about 16 mole percent P₂O₅;

from about 0 to about 25 mole percent CaF₂; and

from about 0 to about 10% B₂O₃, or an equivalent.

Examples of commercially available bioactive glass and their chemicalcomposition include, but not limited to, 45S5: 46.1 mol % SiO₂, 26.9 mol% CaO, 24.4 mol % Na₂O and 2.5 mol % P₂O₅; 58S: 60 mol % SiO₂, 36 mol %CaO, and 4 mol % P₂O₅; S70C30: 70 mol % SiO₂, and 30 mol % CaO, 8.4%Na2O, 40.6% CaO, 39% SiO2, and 12% P2O5.

In one embodiment, the Bioglasses used in the disclosed composition andmethods have the following composition:

SiO₂ in the range of 35 wt. % to 55 wt. %, preferably in the range of 38to 50 mole percent, more preferably in the range 42 wt. % to 47 wt. %,and most preferably 44 wt. % to 46 wt. %;

CaO in the range of 15 wt. % to 40 wt. %, more preferably in the rangeof 18 wt. % to 35 wt. %, more preferably in the range of 22 to 28 wt. %,and most preferably 23 wt. % to 26 wt. %;

Na₂O in the range of 15 wt. % to 40 wt. %, more preferably in the rangeof 18 wt. % to 35 wt. %, more preferably in the range of 22 to 28 wt. %,and most preferably 23 wt. % to 26 wt. %; and

P₂O₅ in the range of 2 wt. % to 10 wt. %, more preferably in the rangeof 3 wt. % to 9 wt. %, more preferably in the range of 4 wt. % to 8 wt.%, and most preferably 5 wt. % to 7 wt. %.

In a particularly preferred embodiment, the Bioglass has the composition45 wt % SiO2, 24.5 wt % CaO, 24.5 wt % Na2O, and 6.0 wt % P2O5.

Thomas et al. [J Long Term Eff Med Implants (2005)15(6):585-97—incorporated herein by reference in its entirety] reviewdifferent bioactive glass materials and their uses. The bioactive glasscompositions suitable for use in accordance with the present disclosureare not limited to the particular examples provided, but include otherbioactive glass materials such as those known in the art. Many bioactiveglass compositions are also disclosed in U.S. Pat. Nos. 5,735,942;6,054,400; 6,171,986; 6,517,857; 9,168,272; and 10,111,814—incorporatedherein by reference in their entirety.

Bioactive and biocompatible glasses have been developed as bonereplacement materials. Studies have shown that these glasses will induceor aid osteogenesis in physiologic systems. The bond developed betweenthe bone and the glass has been demonstrated to be extremely strong andstable. However the size of the particles used to form bone isrelatively large. Tooth dentin is very different from bone. The organiccomponent of dentin (approximately 40%) makes most systems that willbond to bone and tooth enamel ineffective. Most current materials usedfor treatment of tooth desensitization rely on materials that have beenoptimized for the bonding to bone and tooth enamel by their interactionwith the inorganic components. As a result, even the most effectivetreatments are short lived. Therefore, there is a need in the dentalfield for a material that would chemically react with and/or passivatesthe surface of dentin and intimately bonds or adheres to toothstructure, and functions to reduce the reopening of dentin tubules dueto contact with oral fluids.

The bioactive glass used in the toothpaste composition of the inventionis doped with a fluoride compound such as calcium fluoride, sodiummonofluorophosphate (MFP), stannous fluoride, sodium fluoride orcombination thereof. The fluoride-doped bioactive glass comprises afluoride compound in an amount in the range of 0.5 mol. % to 12 mol. %,preferably in the range of 1 mol. % to 10 mol. %, more preferably in therange of 2 mol. % to 7 mol. %, and most preferably 3 mol. % to 6 mol. %.In a particularly preferred embodiment, the Bioglass contains about 5mol. % of the fluoride compound. The toothpaste composition of theinvention contains fluoride-doped bioglass in an amount in the range of0.1% to 8%, preferably in the range of 0.5% to 6%, more preferably inthe range of 1% to 5% and most preferably in the range of 1% to 4% byweight of the total weight of the toothpaste.

The compositions comprising fluoride-doped bioactive glass disclosedherein provide for mechanical and chemical obturation of enamel tubulesas well as anti-caries fluoride ion. Moreover, in certain embodiments,the present compositions and methods optionally provide a bioactivelayer doped with fluoride forming a new structural layer which resultsin long-lasting reduction of tooth hypersensitivity and may function toslowly release the anti-caries fluoride ion to minimize the bacterialpopulation in the mouth. Such structured layers have been observed bythe reformation of a hydroxycarbonate apatite layer on and in dentinsurfaces after treatment with composition comprising bioglass (see forexample US2007/0258916—incorporated herein by reference in itsentirety). Particles that are small enough to fit inside or rest on theopening of the tubules provide for actual physical occlusion of thetubules. Thus, embodiments of the disclosed compositions includeparticles smaller than 90 microns, such particles are more likely toadhere to the tubules or tooth surface because particles less than about90 microns react quickly enough to chemically bond with dentin surfacesand tubules during the use of the disclosed compositions, includingtoothpastes, gels or mouthwashes.

In certain disclosed compositions, the bioglass particles have anaverage diameter of less than about 50 microns, such as less than about20 microns and may fall into a range of from about 0.1 micron to about10 microns, such as an average diameter of about 2 microns. In someembodiments the compositions include particles of many sizes but have atleast about 25% of the particles having a diameter of less than about 5microns, such as less than about 2 microns.

As used herein the phrase “coloring agent” is an agent that imparts notonly color to the toothpaste, but also provides a particular luster orreflectivity such as pearling agents and whiting agents. Coloring agentsinclude, but not limited to, pigments and dyes. A coloring agent mayserve a number of functions, including for example to provide a white orlight-colored coating on a dental surface, to act as an indicator oflocations on a dental surface that have been effectively contacted bythe composition, and/or to modify appearance, in particular color and/oropacity, of the composition to enhance attractiveness to the consumer.Any orally acceptable colorant can be used, including without limitationtalc, mica, magnesium carbonate, calcium carbonate, magnesium silicate,magnesium aluminum silicate, silica, titanium dioxide, red, yellow,brown and black iron oxides, ferric ammonium ferrocyanide, manganeseviolet, ultramarine, titaniated mica, bismuth oxychloride and the like.One or more coloring are optionally present in a total amount by weightin the range of 0.001% to 10%, preferably in the range of 0.01% to 5%,more preferably in the range of 0.1% to 3% of the total weight of thetoothpaste composition.

In a particularly preferred embodiment, the coloring agent is thewhitening agent titanium oxide added to the toothpaste composition in anamount in the range of 0.01 to 5%, preferably in the range of 0.1 to 4%,more preferably in the range of 0.5 to 3%, and most preferably in therange of 1.0% to 2% by weight of the total weight of the toothpastecomposition.

A second aspect of the invention is directed to a method of treating andor controlling teeth hypersensitivity and carries. The method comprisescontacting the toothpaste of the invention with teeth and gum, andbrushing the teeth one or more time per day, preferably at least 2times/day, more preferably at least 4 times/day, and most preferably atleast 5 times per day. In a particularly preferred embodiment, themethod should be carried out after every meal and before bedtime. Thetoothpaste composition should be applied with brushing for at least oneminute, preferably two at least two minutes, and more preferably for atleast three minutes. Not only may the method be used in treatment ofhypersensitivity of the teeth, but also in a maintenance protocol toinsure the long term health of the teeth and gum by preventing plaquebuildup. The protocol may include the use of mouth wash after and/orbefore the application of the toothpaste and frequent visits to adentist office for removal of any accumulated dental plaque andmonitoring the health of the teeth.

EXAMPLE 1

Materials:

The chemicals used were analytical grade. Table 1 lists ingredients ofthe basic composition and the active ingredients as well as theirquantities to formulate dentifrices.

TABLE 1 An Exemplary Composition of Basic and active ingredientsIngredients of basic Composition wt. %¹ Water 36 Sodium Lauryl Sulfate(SLS) 2 Glycerol 32 Sodium Benzoate 1 Methylcellulose 1 CalciumCarbonate 27 Peppermint (Flavoring Agent) 1 Active Ingredient wt. %²Zinc oxide (Nano-powders) 0-3 (Antibacterial/Remineralization)Fluoride-doped bioactive glass 0-4 (Remineralization) Titanium dioxide(Whitening) 0-2 Black cumin oil (Nigella sativa) 0-6(Antibacterial/Anti-inflammatory) ¹Percentage by weight of ingredient inthe total weight of the basic composition. ²Percentage by weight of anactive ingredient in the total weight of the final composition.Methods:

A mixture of basic ingredients was prepared. Active ingredients wereadded to the mixture of basic ingredients and mixed for sufficient timeto insure homogeneity of the mixture. The ratios of the activeingredients are varied to determine the effective amount of eachingredient. The mixing procedure was conducted at ambient temperaturei.e. 23±2° C. One commercial dentifrice i.e. Colgate Cavity Protection(Colgate Palmolive) was used as a reference dentifrice and it containssodium monofluorophosphate 0.76% (0.15% w/v fluoride ion) and dicalciumphosphate dehydrate and was denoted as CT. Table 2 summarizes thecomposition of the toothpastes tested.

TABLE 2 Composition of the Toothpaste Experimental toothpasteComposition Active ingredient² EXT-A ¹Basic composition 1.5 wt. %n-fluoride-doped bioglass containing 5 wt. % fluoride. 3 wt. % n-ZnO. 3wt. % Black seed oil. EXT-B ¹Basic composition 1.5 wt. %n-fluoride-doped bioglass containing 5 wt. % fluoride. 3 wt. % n-ZnO. 3wt. % Black seed oil. EXT-C ¹Basic composition 1.5 wt. %n-fluoride-doped bioglass containing 5 wt. % fluoride. 3 wt. % n-ZnO. 3wt. % Black seed oil. EXT-D ¹Basic composition None CT Active Dicalciumphosphate dehydrate ¹the basic composition is shown in Table 1. ²The wt.% is the percentage by weight of the active ingredient in the totalweight of the toothpaste composition.Teeth Preparation:

Freshly extracted bovine teeth were collected and extracted from cattlehaving an age in the range of 30-72 months old. The age was assessedaccording to Food Safety and Inspection Service (FSIS) standardoperating procedures. All crowns surfaces were intact without cracks,fractures, and occlusal wear. Teeth were scraped clean from soft tissueremnants using a scalpel and currete. Disinfection was performed with 5%sodium hypochlorite for 24 h. Samples were stored in sterile 0.9% saline(ISO 11609:2010) and were stored at 4° C. with 0.5% thymol solution inorder to maintain the mineral content of tooth samples.

Sample Preparation:

Total 60 teeth specimens (4 mm×4 mm×2 mm; length, width and heightrespectively) were prepared from bovine incisors. The crown portions ofthe teeth were sectioned at cementum-enamel junction with a bur undercontinuous flow of water. Coronal portion was used for dentin samples.Specimens were prepared from buccal aspect of the teeth. Water-cooleddiamond bur or disc (MANI, INC. 8-3 Kiyohara Industrial Park,Utsunomiya, Tochigi, Japan) were used for cutting. Plus mark was made atthe back of each tooth with straight fissure bur in order to recognizethe buccal aspect of the tooth. Samples were mounted in the impressioncompound and were labeled after randomly dividing the samples into sixgroups. The specimens were etched with 37% phosphoric acid for 30 s asper specification guidelines, washed and sonicated in distilled waterfor 30 s in order to remove residual particles without affecting thestructure.

Preparation of Reference and Test Paste Slurries:

Reference and test paste slurries were prepared by adding 40 mL ofdistilled water to 25 g of each dentifrice (ISO 11609:2010) and stirredwith a magnetic stirrer. The prepared dentin samples were randomlydivided into 6 groups (n=10). Each tooth was coated with two layers ofacid resistant nail varnish (Max Factor International, Procter & GambleLtd. Surrey, England) except for an exposed dentin window on the buccalsurface.

Testing Apparatus: Brushing Machine:

A custom made tooth brush with six brushing heads, variable speed, andload was used in accordance with the ISO standards (ISO 11609:2010). Itwas used to duplicate the effects of brushing on teeth. The simulatorallowed for accelerated brushing that replicated many years of regulartooth brushing. The samples were subjected to brushing conditions thatclosely resemble the mechanical force and resulting trauma teeth duringnormal brushing. The dentin specimens were positioned in the brushsimulator and a medium tooth brush (Oral B, Flat trim indicator) restedon each specimen with a load of 150 g. The brush moved back and forth (1stroke) and 10,000 brushing cycles were applied on each specimen (ISO11609:2010).

EXAMPLE 2

Characterization

Atomic Force Microscopy (AFM):

Atomic Force Microscope (SPM-9500J3, Shimadzu Corp. Japan) was used forthe assessment of dentin surface roughness. It provided thethree-dimensional surface topography without any sample preparation. Themicroscopy was designed to scan the sample with a probe, measuring thelocal properties such as height, magnetism, and friction. The specimensfrom each group were selected randomly for investigation of AFM aftertreatment. The surface morphology of dentin was observed. Arepresentative sample was selected and micrographs at six differentareas were taken using Atomic Force Microscope equipped with AFMsoftware (SPM-Offline, Shimadzu Corp. Japan). Surface roughness average(Ra) of all the groups with standard and mean deviations was be analyzedby AFM.

Scanning Electron Microscope-Energy Dispersive X-Ray Detector (SEM-EDX):

The surface morphology of the sample was examined by using a ScanningElectron Microscope (TESCAN VEGA-3 LMU, Check Republic). Samples weregold coated in gold SPUTTER COATER (QUORUM). Images were taken in themagnification range from 1500× to 5000× and operated at an acceleratedvoltage of 10-20 kV. Also, energy dispersive X-ray analysis (EDX, OXFORDINSTRUMENTS, UK) was conducted for identification of the abrasiveelements.

Fluoride Release Analysis:

The experimental protocol used in this study was modified from the onesuggested by Pearce [Pearce, E. A laboratory evaluation of New Zealandfluoride toothpastes, The New Zealand dental journal 70(320) (1974)98-108; and Cury et al. Available fluoride in toothpastes used byBrazilian children, Brazilian dental journal 21(5) (2010) 396-400,incorporated herein by reference]. The study was carried out inquadruplicates. About 100 mg toothpastes sample from each group wastaken separately in conical plastic centrifuge tubes which was thenhomogenized in 10 mL deionized water. Then, 5 mL from this suspensionfrom each tube was centrifuged at 6000 rpm for ten minutes to remove theinsoluble fluoride bound to the filler particles. From the extractedelute, 2.5 mL was transferred to two centrifuge tubes. 2.5 mL of twomole hydrochloric acid was then added to each 2.5 mL elute/suspensionwhich was then conditioned at 45° C. for one hour. After adding 5 mL ofone mole sodium hydroxide and one mL TISAB III reagent, the samples wereanalyzed via Ion Selective Electrode (ISE) potentiometry (Hanna HI3222pH/ISE meter and Fluoride electrode) which was pre-calibrated at twopoints (1 ppm and 10 ppm) using fluoride standard solutions.

EXAMPLE 3

Antimicrobial Analysis

Antimicrobial Susceptibility Test (AST):

The test microbial strains i.e. S. mutans (ATCC 25175) and L. casei(ATCC 393) were obtained from American Type Culture Collection (ATCC,Manassas, Va., USA). The dehydrated culture media was purchased fromOxoid™ (Basingstoke, Hampshire, England) and Merck Millipore (Darmstadt,Germany). The culture media were prepared according to the manufacturerinstructions. For the preparation of broths; measured amounts ofdehydrated culture media powder was mixed with measured volume ofdistilled water at required temperature until completely dissolved.Prepared solutions were dispensed into final containers aftersterilization.

For preparation of agar plates, solutions were made according tomanufacturer guidelines. Following sterilization, the freshly preparedsolutions were allowed to cool in a water bath (Anjue, AJ-HHS4, China)at a temperature range of 45-50° C. The cooled solutions were thenpoured into standard 90 mm flat-bottomed petri dishes. In order toensure a standard depth of 4 mm, 20 mL of solution was poured in eachpetri dish. The petri dishes were then left to solidify at roomtemperature for two hours. Following solidification, all plates wereplaced in the refrigerator at 4° C.

In the case of L. casei, chocolate blood agar (CBA) was used. It wasprepared by heating the prepared blood agar solution to an elevatedtemperature of 80° C. The heated solution was then sterilized, cooledand poured into petri dishes for solidification. Prior to conducting theexperiment, all the laboratory equipment were sterilized in an autoclaveat a temperature of 121° C., pressure of 15 psi, for 15 min. Samesterilization protocol was followed for dentifrices and molten culturemedia solutions before dispensing them into final containers.

Preparation of Dentifrices:

Three dilutions of each dentifrice were made with distilled water in theratio 1:1, 1:2 and 1:4 respectively. Dentifrice slurries were vortexedin an electric shaker (Heidolph REAX 2000) and introduced in labeled,plastic containers.

Agar Well-Diffusion Assay:

Direct colony suspension method was used, according to EUCASTguidelines, for the preparation of inoculums. It involved preparingsaline suspensions of isolated colonies, selected from overnight growthculture plates. Three to five well-isolated, similar colonies wereselected and transferred to tubes containing 5 mL of 0.9% normal saline.The tubes were vortexed (Heidolph REAX 2000). To standardize theinoculum preparations for susceptibility testing, the suspensions wereadjusted to a density equivalent to 0.5 Standard of the McFarlandTurbidity Scale. This was done by visual comparison to McFarlandturbidity standards kit and by using a photometric device (DensiCHEKplus, bioMérieux Inc., N.C., USA). Visual comparison was carried outagainst a white background. In this way, adjusted inoculum of both thebacterial strains S.mutans ATCC 25175 and L. casei ATCC 393 wereprepared.

Inoculation of the Agar Plates:

Within fifteen minutes of the preparation of the adjusted inoculumsuspensions, a sterile cotton swab was dipped in the respective tubes.The excess fluid was removed by pressing the swab against the wall ofthe tube. The inoculum was spread evenly over the entire surface of therespective agar plates of prepared media to create a bacterial lawn. Theplates were rotated thrice at an angle of 60°, so that swabbing wasaccomplished evenly in three directions.

Measurement of Zones of Inhibition:

Following incubation, the resultant zones of inhibition were observed onthe agar plates. These appeared as clear, circular halos surrounding thewells. The assessment of anti-cariogenic potential was done by recordingthe diameters of ZOI (mm). As the test was conducted in triplicate; meanvalues were calculated for each.

EXAMPLE 3

Determination of Roughness Caused by the Experimental Toothpastes

Atomic Force Microscopy (AFM):

Surface roughness was assessed using 3D-Atomic Force Microscope(SPM-9500J3, Shimadzu Corp, Japan) operating in non-contact mode. Theroughness average (Ra) is the most widely used one dimensional (1D)roughness parameter, and denotes the arithmetic mean of the absolutevalues of the collected roughness data points. The surface of all groupsshowed signs of abrasion even when the brush was used with distilledwater. Typical 3D images of abraded (after toothbrush simulation) andnon-abraded dentin (polished surface) is illustrated in FIG. 1 .3D-images were reported in area selection of 10.0×10.0 μm.

The untreated portion (polished surface) presented relatively low valuesof surface roughness. However, as expected toothbrush abrasion causedvisible nanoscale alterations on the surface of all samples to varyingextent dependent on the toothpaste employed as illustrated by AFM3D-images. The negative control group (distilled water) showed the leastsurface roughness, whereas the EXT-C group showed the highest surfaceroughness. The EXT-A & B groups showed slightly more surface roughnesswhen compared to positive control group (Colgate cavity protectionslurry), whereas EXT-D group (without abrasives) produced lesser surfaceroughness than positive control group.

Surface Roughness Average (Ra) Analysis by AFM

The results for the surface roughness average (Ra) with means andstandard deviation of all groups are summarized in Table 2.

TABLE 3 Descriptive Analysis and Normality test of Ra StandardKolmogorov Group Mean (nm) Deviation Smirnov Sig Remarks Distilled(Negative 9.0833 1.03425 0.981 Normal Control) CT 26.8167 1.05341 0.875Normal EXT-A 28.3667 1.77388 0.577 Normal EXT-B 32.2833 1.47705 0.906Normal EXT-C 44.5333 3.93277 1 Normal EXT-D 20.7667 1.15873 0.999 Normal

ANOVA test for the results in Table 3 was highly significant withp-value=0.000 and show that the results of the six experiments weresignificantly different in mean Ra. Kolmogorov Smirnov test indicatedthat the results of the six experiments followed normal distribution assuch data are suitable to apply one way ANOVA. Leven's test ofhomogeneity of variance was significant with p-value=0.021. It indicatedthat variances of Ra of the above six experiments were not homogeneous.For one-to-one comparison, multiple comparison tests were performed byTukey's and Tamhane's tests. Since Tukey's test is not advised in casevariances of groups are not homogenous, Tamhane's test was alsoperformed which is more robust in case of non-homogenous variances. Thefindings from both tests were quite similar. As per Tukey's results allexperiments were significantly different from each other withp-value<0.05 except Colgate (Positive Control group) and Experimentalpaste A, there was no significant difference between the Colgatepositive control and EXT-A with p-value=0.764.

The findings from Tamhane's test were quite similar that all groups weresignificantly different from each other with p-value<0.05 except Colgate(Positive Control group) and Experimental paste A, there was nosignificant difference between these two groups with p-value=0.802.

Relative Dentin Abrasivity (RDA) Calculation of the Experimental Pastes

EXT-A

According to the ISO 11609:2010(E)

${RDA}_{test} = \frac{{Ra}_{test} \times {RDA}_{ref}}{{Ra}_{ref}}$

Where RDA_(ref) is 70 (known value), Ra_(test) is 28.3667 (measuredvalue), and Ra_(ref) is 26.8167 (measured value).

The resulting value of RDA_(test) is 74.04.

EXT-B

According to the ISO 11609:2010(E)

${RDA}_{test} = \frac{{Ra}_{test} \times {RDA}_{ref}}{{Ra}_{ref}}$

Where RDA_(ref) is 70 (known value), Ra_(test) is 32.2833 (measuredvalue), and Ra_(ref) is 26.8167 (measured value).

The resulting value of RDA_(test) is 84.26

EXT-C

According to the ISO 11609:2010(E).

${RDA}_{test} = \frac{{Ra}_{test} \times {RDA}_{ref}}{{Ra}_{ref}}$

Where RDA_(ref) is 70 (known value), Ra_(test) is 44.5333 (measuredvalue), and Ra_(ref) is 26.8167 (measured value).

The resulting value of RDA_(test) is 116.24.

EXT-D

According to the ISO 11609:2010(E)

${RDA}_{test} = \frac{{Ra}_{test} \times {RDA}_{ref}}{{Ra}_{ref}}$

Where RDA_(ref) is 70 (known value), Ra_(test) is 20.7667 (measuredvalue), and Ra_(ref) is 26.8167 (measured value).

The resulting value of RDA_(test) is 54.20.

EXAMPLE 4

SEM Analysis of Morphology

SEM analysis was performed to assess the surface morphology. Surfacemorphology of the etched dentin is given in FIG. 2 showing open orpatent dentinal tubules. FIGS. 3A-3F show SEM micrographs for simulatedbrushing with distilled water (negative control), Colgate cavityprotection slurry (positive control), and experimental pastes A, B, Cand D slurries for samples rinsed with deionized water followed bysonication for 10 sec.

SEM micrographs of etched dentin with 37% phosphoric acid for 30 secshowed open or patent dentinal tubules. Control samples which wererinsed with deionized water followed by sonication for 10 sec, andbrushing with distilled water showed smooth dentin surface with open orpatent dentinal tubules and some particles on dentin surface. Also,positive control samples brushed with Colgate cavity protection slurryshowed relatively smooth dentin surface with open or patent dentinaltubules and few particles on the dentin surface and some were partiallyobliterated. SEM micrographs of samples brushed with experimental pasteA slurry showed a smear layer like coating covering all the dentinsurface and uniform occlusion of almost all the dentinal tubules. Veryfew tubule orifices remained partially opened with maximum narrowing oftubular lumen. Also experimental paste B slurry produced a smear layerlike coating covering the entire dentin surface that completely occludedalmost all the dentinal tubules. Micrographs of experimental pasteslurry C showed similar results with uniform occlusion of almost all thedentinal tubules by a smear layer like coating and only a few tubuleorifices showed partial obliteration with maximum narrowing of thetubular lumen. Experimental paste slurry D showed relatively smoothsurface with open dentinal tubules with the presence of few particles ondentin surface and some were partial obliterated.

The result in FIG. 2 clearly shows that the untreated itched tooth showstubules having dimeters in the range of about 1 to 5 μm. Upon treatmentwith the experimental compositions A-D the tubules occluded at least by40%, at least 50%, at least 60%, at least 70%, at least 80%, at least90%, and even some were completely occluded with some having an openingin the range of less than 1 to 2 μm, compare FIGS. 3A to 3E and 3F.

Elemental Analysis by SEM-EDX

EDX analysis commenced on the etched dentin surface showed large amountsof carbon and oxygen. Calcium, phosphate and sodium were rarelyobserved. The most common elements detected in samples brushed withdistilled water were carbon and oxygen. Colgate cavity protectiontreatment showed large amounts of carbon and oxygen while only traceamounts of calcium, silicon and sodium. However in samples treated withexperimental pastes A, B and C calcium and phosphate became the dominantelements including the presence of silicon, sodium, fluoride and zincwhile experimental paste D without abrasives showed high amounts ofcarbon and oxygen with only trace amounts of calcium, phosphate, sodiumand silicon. Particle size analysis of samples treated with experimentalpastes A, B and C showed attachment of nano-sized fluoride containingbioactive particles and nano-oxides occluding almost all the dentinaltubules and maximum narrowing of tubular lumen in few remaining tubules(remineralization) at magnifications of ×10000 and EDX confirmed theattachment of dentin like structure.

EXAMPLE 5

Fluoride Release Analysis

Both elutes and suspensions of the commercial toothpaste showed fluoriderelease of 6.55 ppm in elutes and 6.28 ppm in suspensions. Maximum meanfluoride release (FR) exhibited by suspensions of the experimentaltoothpastes in descending order was as follows: EXT-C (14.16 ppm), EXT-B(11 ppm), and EXT-A (3.52 ppm). Maximum mean FR exhibited by elutes ofthe experimental toothpastes given in descending order was as follows:EXT-B (10.79 ppm), EXT-C (9.95 ppm), and EXT-A (9.64 ppm).

EXAMPLE 6

Antimicrobial Analysis

Antimicrobial Susceptibility Test (AST)

Characteristic zones of inhibition were visible for the experimental andcommercial dentifrices, when tested against the microbial strains S.mutans and L. casei, under different conditions. Zones of inhibitionagainst S. mutans appeared after 24 h; whereas in the case of L. casei,the zones were visible after 48 h. Mean values (n=3) and standarddeviations of diameters of zones of inhibition (mm) recorded forexperimental and commercial dentifrices against S. mutans are L. caseiare summarized in Table 3 and 4 respectively. CT was found to have thehighest inhibition zone against both microbial strains, at alldilutions, however the difference was insignificant.

TABLE 3 Zone of inhibition shown by various toothpastes withLactobacillus casei Measurement of Zones of inhibition (mm) Dilution 1:1Dilution 1:2 Dilution 1:4 Dentifrice Mean SD Mean SD Mean SD EXT-A 20.50.408 18.17 0.623 17 0.816 EXT-B 25.33 0.471 22.33 0.943 20.17 0.624EXT-C 26.1 0.535 23.17 1.027 21.67 0.471 CT 26.33 0.942 23.06 1.715 211.632

TABLE 4 Zone of inhibition shown by various toothpastes with S. mutansMeasurement of Zones of inhibition (mm) Dilution 1:1 Dilution 1:2Dilution 1:4 (1 g/ml) (1 g/2 ml) (1 g/4 ml) Dentifrice Mean SD Mean SDMean SD EXT-A 21.17 1.027 16.5 0.408 15.83 0.236 EXT-B 23.67 0.471 190.816 16.67 0.943 EXT-C 25.33 0.849 21 0.816 18.83 0.624 CT 26 1.632 230.816 19.83 0.236

The invention claimed is:
 1. A method of controlling dental caries andtreating teeth sensitivity, comprising: applying a toothpastecomposition to teeth, and brushing the teeth for a time of at least oneminute; wherein the toothpaste composition comprises: (a) Nigella sativaoil in an amount of 3 wt. %; (b an amount of water in the range of 33wt. % to 36 wt. %; (c) sodium lauryl sulfate in the range of 1 wt. % to2 wt. %, (d) glycerol in the range of 29 wt. % to 32 wt. %, (e) sodiumbenzoate in the range of 0.5% to 1.0 wt. %, (f) methyl cellulose in therange of 0.5% to 1.0 wt. %, (g) calcium carbonate in the range of 24 wt.% to 27 wt. %, (h) flavoring agent in the range of 0.5% to 1.0 wt. %,(i) fluoride-doped bioactive glass in an amount of 1.5 wt. %; (j) zincoxide in an amount of 3.0 wt. %; and (k) titanium oxide in an amount of2 wt. %; wherein the wt. % is present by weight of the total weight ofthe toothpaste and the toothpaste composition has a maximum meanbioglass fluoride release in elutes of 9.95 to 10.75 ppm.
 2. The methodof claim 1, wherein the toothpaste comprises water in an amount of about36 wt. % of the total weight of the toothpaste.
 3. The method of claim1, wherein the sodium lauryl sulfate is present in an amount of 2 wt. %of the total weight of the toothpaste.
 4. The method of claim 1, whereinthe sodium benzoate is present in an amount of about 1 wt. % of thetotal weight of the toothpaste.
 5. The method of claim 1, wherein theflavoring agent is present in an amount of about 1 wt. % of the totalweight of the toothpaste.